Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant phenotype of human tumor cell lines
Perego, P. ; Righetti, S. C. ; Supino, R. ; Delia, D. ; Caserini, C. ; Carenini, N. ; Bedogné, B. ; Broome, E. ; Krajewski, S. ; Reed, J. C. ; Zunino, F.
Springer
Published 1997
Springer
Published 1997
| ISSN: |
1573-675X
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|---|---|
| Keywords: |
Apoptosis ; bcl-2 ; cisplatin resistance ; p53
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| Source: |
Springer Online Journal Archives 1860-2000
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| Topics: |
Biology
Medicine
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| Notes: |
Abstract Since apoptosis is the primary mode of cell death induced by cisplatin, the role of apoptosis and apoptosis-related gene products in cisplatin resistance was investigated in four human cisplatin-resistant cell lines of different tumour type. A common feature of the resistant sublines was a reduced susceptibility to drug-induced apoptosis compared to parental sensitive lines. Loss of wild-type p53 function was not a general event associated with the development of drug resistance. An increased bcl-2 expression was found in resistant cells characterized by mutant p53 (A431/Pt and IGROV-1/Pt), whereas in osteosarcoma (U2-OS/Pt) and in ovarian carcinoma (A2780/CP) cells with wild-type p53, bcl-2 levels were markedly reduced. U2-OS/Pt cells had a 16-fold increase in the level of Bcl-xL protein. Stable transfection of U2-OS cells with bcl-xL cDNA conferred a low level of drug resistance to cisplatin, suggesting that overexpression of this gene contributes to the ci splatin-resistant phenotype of this osteosarcoma cell system. In conclusion, these observations suggest a variable contribution of apoptosis-related genes to cisplatin resistance depending on the biological background of the cell system and presumably reflecting different pathways of apoptosis.
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| Type of Medium: |
Electronic Resource
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| URL: |